U.S. Pat. No. 4,133,814 teaches a variety of compounds that may be prepared by the process of this invention. That patent describes the use of phenacyl, halophenacyl, and alkyl protecting groups. The processes descibed therein do not, however, suggest the particularly advantageous way to use the methyl protecting group which is provided by this invention.
Chem. Lett. 97-98 (1979), Tet. Let. 5211-14 (1978), and J. Org. Chem. 45: 4275-77 (1980) disclosed the use of aluminum halide thiols as reagents for the demethylation of various aliphatic and aromatic ethers.
U.S. Pat. No. 4,380,635 teaches the preparation of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-aminoethoxy)benzoyl]benzo[b]thiophen es. The patent describes the acylation of a benzothiophene in the presence of aluminum chloride or bromide with an acid chloride or bromide followed by the addition of a sulfur compound to cleave the methoxy ether linkages, which finally affords 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-aminoethoxy)benzoyl]benzo[b]thiophen es upon hydrolytic work-up. Specific sulfur compounds disclosed as useful for cleaving the methoxy protecting groups include methanethiol, ethanethiol, isopropanethiol, butanethiol, diethyl sulfide, dibutyl sulfide, ethyl propyl sulfide, butyl isopropyl sulfide, dimethyl sulfide, methyl ethyl sulfide, methyl phenyl sulfide, ethyl phenyl sulfide, butyl phenyl sulfide, benzenethiol, and methionine. Ethanethiol is identified as the preferred agent, and all but two of the examples provided herein utilize this particular thiol. The other thiols employed are dimethyl sulfide and methionine. Methyl ether cleavage was not complete with methionine. Instead, the reaction mixture consisted primarily of a mixture of the two possible monomethyl ether products.
U.S. Pat. No. 4,948,829 discloses 2-methyl-5-t-butyl benzenethiol as a stabilizer of vinyl chloride polymers. Many of the benzothiophene compounds prepared by the process of the instant invention are described in U.S. Pat. No. 4,133,814.
A major disadvantage of previous processes described in the art is the odor associated with the sulfur compounds employed, and with the sulfur containing by-products which are generated in the process. The threshold of human detection for ethanethiol is 0.47 ppb. The odor is a primary deterrent to large scale manufacture of many commercially significant benzothiophenes using processes known in the art.
Thus, it would be a significant contribution to the art to provide processes for the preparation of benzothiophenes which employ essentially odorless sulfur compounds.